1,2,3,4-tetrahydro-6,7-dimethoxy-2-<3-<(4-nitrophenyl)oxy>propyl>isoquinoline | 143665-30-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1,2,3,4-tetrahydro-6,7-dimethoxy-2-<3-<(4-nitrophenyl)oxy>propyl>isoquinoline
• 英文别名: 1,2,3,4-Tetrahydro-6,7-dimethoxy-2-[3-(4-nitrophenoxy)propyl]isoquinoline；6,7-dimethoxy-2-[3-(4-nitrophenoxy)propyl]-3,4-dihydro-1H-isoquinoline
• CAS: 143665-30-9
• 化学式: C₂₀H₂₄N₂O₅
• 分子量: 372.421
• InChiKey: QEJSOKNMABMFNG-UHFFFAOYSA-N

物化性质

• 沸点：
  550.7±50.0 °C(Predicted)
• 密度：
  1.202±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  76.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1,2,3,4-tetrahydro-6,7-dimethoxy-2-<3-<(4-nitrophenyl)oxy>propyl>isoquinoline 在 palladium on activated charcoal 氢气 、 1-羟基苯并三唑一水物 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 生成 9,10-Dihydro-9-oxo-N-[4-[3-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)propoxy]phenyl]-4-acridinecarboxamide
  参考文献：
  名称：

  Synthesis and Activity against Multidrug Resistance in Chinese Hamster Ovary Cells of New Acridone-4-carboxamides

  摘要：

  A number of tricyclic carboxamides have been synthesized and tested to evaluate their ability to reverse multidrug resistance in the (CHC)-C-R/5 cell line. Among them the acridone derivatives were the most potent, A key feature is the presence of a dimethoxybenzyl or phenethylamine cationic site, separated from the tricyclic lipophilic part by a carbamoylphenyl chain. Optimization led to compounds 2 orders of magnitude more active than the prototype inhibitors verapamil and amiodarone. On the basis of in vitro and in vivo activities, 9,10-dihydro-5-methoxy- 9-oxo-N-[4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxyisoquinol-2-yl)ethyl]phenyl]-4-acridinecarboxamide (84) has been selected for further development.

  DOI：

  10.1021/jm00013a017
• 作为产物：
  描述：

  6,7-二甲氧基-1,2,3,4-四氢异喹啉 在 potassium fluoride on Celite 、 sodium hydride 作用下， 以 氘代二甲亚砜 、 乙腈 为溶剂， 反应 21.0h， 生成 1,2,3,4-tetrahydro-6,7-dimethoxy-2-<3-<(4-nitrophenyl)oxy>propyl>isoquinoline
  参考文献：
  名称：

  Synthesis, electrophysiological properties and analysis of structural requirements of a novel class of antiarrhythmic agents with potassium and calcium channel blocking properties

  摘要：

  Class III antiarrhythmic agents have been shown to prevent reentrant arrhythmias but also to be responsible for initiating arrhythmias characterised by afterdepolarizations and triggered activities. By combining potassium and calcium channel antagonistic actions, as with BRL-32872(1,2) (1), it might be possible to reduce the incidence of proarrhythmias albeit retaining antiarrhythmic efficacy. In the present study we synthesised and tested for their electrophysiological activity in guinea pig papillary muscle a wide panel of analogues of BRL-32872. Some qualitative relationships between compound structure and the inhibitory effect on the rapidly activating component of the delayed rectifier potassium current and/or the L-type calcium current will be presented. New derivatives depicting bell-shaped dose-response curves on action potential duration may therefore represent novel agents for improved antiarrhythmic therapy. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)00166-7

文献信息

• Acridine derivatives
  申请人：Laboratoires Glaxo SA

  公开号：US05604237A1

  公开（公告）日：1997-02-18

  These are provided compounds of formula I ##STR1## wherein A represents an oxygen or a sulphur atom, a bond or a group (CH.sub.2).sub.1 NR.sup.9 (where 1 represents zero or 1 and R.sup.9 represents a hydrogen atom or a methyl group); B represents a C.sub.1-4 alkylene chain optionally substituted by a hydroxyl group, except that the hydroxyl group and moiety A can not be attached to the same carbon atom when A represents an oxygen or sulphur atom or a group (CH.sub.2).sub.1 NR.sup.9, or when A represents a bond B may also represent a C.sub.2-4 alkenylene chain; R.sup.3 represents a hydrogen atom or a C.sub.1-4 alkyl group; m represents 1 or 2; R.sup.7 represents a hydrogen atom or R.sup.3 and R.sup.7 together form a group --(CH.sub.2).sub.n -- where n represents 1 or 2. These compounds can sensitize multidrug-resistant cancer cells to chemotherapeutic agents and may be formulated for use in therapy, particularly to improve or increase the efficacy of an antitumor drug.

  这些化合物的化学式为I ##STR1## 其中A代表氧原子或硫原子，键或基团(CH.sub.2).sub.1 NR.sup.9 (其中1代表零或1，R.sup.9代表氢原子或甲基基团)；B代表C.sub.1-4烷基链，可选择性地被羟基取代，但当A代表氧原子或硫原子或基团(CH.sub.2).sub.1 NR.sup.9时，羟基和基团A不能附加在同一碳原子上，或当A代表键时，B也可以代表C.sub.2-4烯基链；R.sup.3代表氢原子或C.sub.1-4烷基基团；m代表1或2；R.sup.7代表氢原子或R.sup.3和R.sup.7一起形成一个基团--(CH.sub.2).sub.n--，其中n代表1或2。这些化合物可以使多药耐药癌细胞对化疗药物产生敏感性，可以用于治疗，特别是用于提高或增加抗肿瘤药物的疗效。
• Direct tritium labeling of multifunctional compounds using organoiridium catalysis. 2.
  作者：A. Y. L. Shu、D. Saunders、S. H. Levinson、S. W. Landvatter、A. Mahoney、S. G. Senderoff、J. F. Mack、J. R. Heys

  DOI：10.1002/(sici)1099-1344(199908)42:8<797::aid-jlcr240>3.0.co;2-o

  日期：1999.8

  A variety of complex compounds have been labeled with tritium gas by catalytic exchange in the presence of catalyst precursors [(cod)Ir(dppe)]BF4 or [(cod)Ir(py)(PCy3)]BF4. In most cases, predictable regioselectivity and high specific activities are achieved. These results are compared in some cases to the results of labeling related compounds with [(cod)Ir(PPh3)(2)]BF4. Prereduction of the catalyst precursors in situ with hydrogen allows the use of smaller quantities of tritium gas and reduces the amount of radioactive waste. Two or more compounds can be labeled simultaneously as mixtures then separated in the HPLC purification step to increase compound throughput.
• ACRIDINE DERIVATIVES
  申请人：LABORATOIRES GLAXO SA

  公开号：EP0569380B1

  公开（公告）日：1997-05-28
• US5604237A
  申请人：——

  公开号：US5604237A

  公开（公告）日：1997-02-18
• Synthesis and Activity against Multidrug Resistance in Chinese Hamster Ovary Cells of New Acridone-4-carboxamides
  作者：Nerina Dodic、Bernard Dumaitre、Alain Daugan、Pascal Pianetti

  DOI：10.1021/jm00013a017

  日期：1995.6

  A number of tricyclic carboxamides have been synthesized and tested to evaluate their ability to reverse multidrug resistance in the (CHC)-C-R/5 cell line. Among them the acridone derivatives were the most potent, A key feature is the presence of a dimethoxybenzyl or phenethylamine cationic site, separated from the tricyclic lipophilic part by a carbamoylphenyl chain. Optimization led to compounds 2 orders of magnitude more active than the prototype inhibitors verapamil and amiodarone. On the basis of in vitro and in vivo activities, 9,10-dihydro-5-methoxy- 9-oxo-N-[4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxyisoquinol-2-yl)ethyl]phenyl]-4-acridinecarboxamide (84) has been selected for further development.